| 李 洋,史 策,杨东光,卫 佳,王振坤,张 鑫.γ-生育三烯酚联合亚砷酸对急性早幼粒细胞NB4生长的抑制作用及机制[J].,2018,(5):812-816 |
| γ-生育三烯酚联合亚砷酸对急性早幼粒细胞NB4生长的抑制作用及机制 |
| Inhibitory Effect and Mechanism of γ-tocotrienol in Combination with Arsenic Trioxide on the Growth of Acute Promyelocytic Leukimia Cell Line NB4 |
| 投稿时间：2017-12-06 修订日期：2017-12-28 |
| DOI：10.13241/j.cnki.pmb.2018.05.003 |
| 中文关键词: γ-生育三烯酚 亚砷酸 NB4细胞 凋亡 caspase-3 |
| 英文关键词: γ-tocotrienol ATO NB4 Apoptosis Caspase-3 |
| 基金项目:国家自然科学基金项目（81402666）；中国博士后面上项目（2015M571447）；黑龙江省博士后基金项目（Z14150）；哈尔滨医科大学创新科学研究资助项目（2016LCZX47） |
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| 中文摘要: |
| 摘要 目的：研究γ-生育三烯酚联合亚砷酸对急性早幼粒细胞NB4生长的抑制作用及可能的分子机制。方法：采用CCK-8、细胞周期实验检测细胞增殖、利用激光共聚焦显微镜、Annexin V/PI染色、Caspase活性检测、Western Blot等方法测定细胞凋亡。采用1 μmol/L ATO及不同浓度(0、15、30、45 μmol/L)的γ-生育三烯酚处理NB4细胞24、48和72小时，通过CCK-8检测细胞的增殖情况，流式细胞术、激光共聚焦显微镜检测细胞周期和凋亡情况，检测Caspase3，8，9的活性，Western Blot检测细胞中c-cas- pase-3、Bcl-2 和survivin的蛋白表达。结果：γ-生育三烯酚联合亚砷酸显著抑制NB4细胞增殖(P<0.01)，且随着作用时间延长和γ-生育三烯酚浓度的增加，其增殖抑制作用增强；细胞周期阻滞在S期，S期的比例由38.21%±2.99上升到50.31%±5.03；γ-生育三烯酚联合亚砷酸诱导NB4细胞凋亡，1 μmol/L ATO联合15、30 ?滋mol/L的γ-生育三烯酚处理48h后，细胞活率分别为82.27% ±3.16、66.97% ±3.17、12.63% ±2.66；1 μmol/L ATO联合30 μmol/L的γ-生育三烯酚处理后，NB4细胞caspase-3，-8，-9的活性均较ATO单独用药组显著增高，c-caspase-3表达增高而Bcl-2 和survivin蛋白的表达无明显变化。结论：生育三烯酚联合亚砷酸对急性早幼粒细胞NB4的生长具有抑制作用，此作用可能与抑制增殖并诱导凋亡相关，其作用靶点可能与促进Cas- pase诱导的凋亡有关。 |
| 英文摘要: |
| ABSTRACT Objective: To evaluate the inhibitory effect and possible mechanism of γ-tocotrienol in combination with ATO on the acute promyelocytic leukimia cell line NB4. Methods: NB4 cells were treated with 1 μmol/L ATO in combination with different concen- trations of γ-tocotrienol(15, 30and45 μmol/L) for 24, 48, 72h respectively. The proliferation of NB4 cells were tested by CCK-8 assay. Flow cytometry and Confocal microscopy were used to evaluate the cell cycle and apoptosis of γ-tocotrienol in combination with ATO on NB4 cells. The activity of Caspase3, 8, 9 and the protein expression of c-caspase-3, Bcl-2 and survivin were evaluated by Western Blot. Results: ATO in combination with different concentrations of γ-tocotrienol significantly suppressed proliferation on NB4 cells. The cell cycle arrested at the S phase, The proportion at the S phase from 38.21 %±2.99 to 50.31%±5.03 compared with 1 μmol/L ATO treated cells. Various apoptotic assessment assays have shown that combination of ATO and γ-tocotrienol significantly induced apoptosis in a dose-dependent manner in NB4 cells.The cell viability was 82.27%±3.16, 66.97%±3.17, 12.63%±2.66 in NB4 cells treated with 1 μmol/L ATO and in combination with 15, 30 μmol/L γ-tocotrienol for 48 h, respectively. In addition, caspase activity assay and western blot have shown that ATO + γ-tocotrienol induced apoptosis in NB4 cells by activation of caspase-3,-8, and-9. However, γ-tocotrienol had no significant effect on Bcl-2 and survivin expression. Conclusion: These data suggest that γ-tocotrienol as a poten- tial, new support treatment for the APL patients. Moreover, caspase-3 could be a promising target for γ-tocotrienol in an effective method of chemopreven- tion and chemotherapy in APL patients. |
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